HealthDay News — Use of a vaginal integrase inhibitor-containing gel provided pre-exposure and post-exposure prophylaxis (PREP/PEP) against vaginal HIV infection in a macaque model, results of a proof-of-concept study published in Science Translational Medicine indicate.
Charles Dobard, PhD, from the CDC in Atlanta, and colleagues determined the kinetics of strand transfer of integrase inhibitors in vitro. A repeat-challenge macaque model was used to investigate the efficacy of vaginal gels containing integrase strand transfer inhibitors applied prior to or after simian/human immunodeficiency virus (SHIV) challenge.
Based on the kinetics of strand transfer, the researchers confirmed that integration began about six hours after infection. In the macaque model, a gel containing the strand transfer inhibitor L-870812 applied 30 minutes before SHIV challenge protected two of three macaques.
A 1% raltegravir gel also protected macaques when applied three hours post-SHIV exposure (five of six protected; P< 0.05). Despite continued gel dosing after infection, breakthrough infections exhibited no evidence of drug resistance in plasma or vaginal secretions. Vaginal absorption was rapid, reflecting a short pharmacological lag time.
In breakthrough infections after raltegravir gel treatment, there was a substantial reduction in vaginal, but not plasma, virus load.
“We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or three hours after virus exposure,” the authors write.
Two authors are named on a patent application relating to inhibition of HIV infection through chemoprophylaxis.